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Gastrointestinal Imaging |
1 From the Department of Radiology, University of Wisconsin Medical School, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252 (P.J.P.); Department of Radiology, National Naval Medical Center, Bethesda, Md (P.J.P.); Department of Radiology and Nuclear Medicine, Uniformed Services University of the Health Sciences, Bethesda, Md (P.J.P.); Departments of Radiology (J.R.C.) and Gastroenterology (I.H.), Walter Reed Army Medical Center, Washington, DC; and Department of Gastroenterology (W.R.S.), Naval Medical Center, San Diego, Calif. Received October 4, 2003; revision requested November 21; final revision received February 4, 2004; accepted February 17. Supported in part by Department of Defense Advances in Medical Practice funds. Address correspondence to P.J.P. (e-mail: ppickhardt@mail.radiology.wisc.edu).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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MATERIALS AND METHODS: A total of 1233 asymptomatic adults (mean age, 57.8 years; 505 women, 728 men) underwent same-day CT colonography and optical colonoscopy procedures. CT colonoscopy studies were interpreted prospectively with a primary three-dimensional approach immediately before optical colonoscopy. Statistical analysis was performed with the 
2 test. Size, prevalence, and by-polyp detection differences were compared between adenomatous and nonadenomatous polyps.
RESULTS: Seven hundred fifty-six (57.7%) colorectal polyps identified at optical colonoscopy in 410 (33.3%) patients were nonadenomatous; of these lesions, 622 (82.3%) were diminutive (
5 mm). Nonadenomatous polyps accounted for 622 (64.4%) of 966 diminutive lesions and 134 (39.9%) of 344 polyps 6 mm or larger (P < .001). The prevalence rate for nonadenomatous polyps was 8.8% (109 of 1233 patients) and 2.0% (25 of 1233 patients) at 6- and 10-mm thresholds, respectively. CT colonography by-polyp sensitivity for nonadenomatous lesions was 73.1% (98 of 134 patients) and 73.3% (22 of 30 patients) at 6- and 10-mm thresholds, respectively, compared with 85.7% (180 of 210 patients) and 92.2% (47 of 51 patients) for adenomas (P < .01). In 1065 patients that did not have a 6-mm or larger adenoma at optical colonoscopy, CT colonography depicted a nonadenomatous polyp that was 6 mm or larger in 63 (5.9%) patients and a nonadenomatous polyp that was 10 mm or larger in 15 (1.4%) patients.
CONCLUSION: More than 80% of nonadenomatous polyps were diminutive, but they accounted for nearly 40% of polyps that were 6 mm or larger. Fortunately, CT colonography is significantly (P < .01) less sensitive in the detection of lesions that have no malignant potential when compared with similar-sized adenomas that have malignant potential.
Index terms: Colon neoplasms, 75.3111, 75.3113 • Colon neoplasms, CT, 75.12119 • Colon neoplasms, diagnosis, 75.3111, 75.3113 • Colonoscopy, 75.12119
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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5 mm), which explains why polyp size serves as the primary surrogate for histologicanalysis with CT colonography and optical colonoscopy (5). Despite this fact, the actual prevalence of nonadenomatous lesions that are 6 mm or larger in a screening population is not well established (5). This information is important, however, because optical colonoscopy referral for polypectomy of a lesion detected at CT colonography that is ultimately proved to be nonadenomatous is of no real benefit to the patient. This issue of nonadenomatous polyps has been less critical with optical colonoscopy screening because it serves both diagnostic and therapeutic roles; hence, there is not an additional referral procedure hanging in the balance. The purpose of our study was to use CT colonography to prospectively investigate the prevalence and size distribution of nonadenomatous polyps in asymptomatic adults and compare detection rates of adenomatous and nonadenomatous polyps.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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A total of 1233 consecutive asymptomatic adults (mean age, 57.8 years; age range, 40–79 years) successfully underwent same-day CT colonography and optical colonoscopy within a 14-month period. Of the 1233 asymptomatic adults, 1201 were categorized as being at average risk for colorectal neoplasia by virtue of satisfying the exclusion criteria listed previously and lacking any notable family history of colorectal cancer (6). This study included 505 women (mean age, 58.1 years; age range, 42–79 years) and 728 men (mean age, 57.7 years; age range, 40–79 years).
CT Colonography and Interpretation
Study participants underwent colonic cleansing with oral intake of 90 mL of phosphosoda and 10 mg of bisacodyl the day before CT colonography and optical colonoscopy. Patients also consumed 500 mL of dilute barium (2.1% wt/wt) and 120 mL of water-soluble iodinated contrast material (Gastrografin; Bracco Diagnostics, Princeton, NJ) for the purposes of stool tagging and electronic fluid subtraction, as described previously (7). Our CT protocol and CT colonography interpretation technique has also been described previously (1). To summarize, colonic distention was achieved with patient-controlled insufflation of room air by means of a standard hand-held enema bulb attached to a small flexible rectal catheter by a short segment of enema tubing. CT scans were acquired with patients in the supine and prone positions with breath holding by using four- and eight-channel multi–detector row CT scanners (LightSpeed Plus and LightSpeed Ultra; GE Medical Systems, Milwaukee, Wis). The CT technique entailed 1.25–2.50-mm collimation, 13.5–15.0 mm/sec table speed, 1-mm reconstruction interval, 100 mAs (effective), and 120 kVp. The estimated effective radiation dose for the four-channel CT protocol was approximately 8.3 mSv.
Prospective interpretation of CT colonography studies was performed by using a commercially available CT colonography system (V3D Colon, version 1.2; Viatronix, Stony Brook, NY). This system isolates the colon, electronically subtracts any residual opacified fluid, and generates an automated centerline as routine postprocessing steps; this requires approximately 10 minutes but occurs before any radiologist interaction. The three-dimensional endoluminal "fly-through" scans were used for primary polyp detection, and the two-dimensional scans were used mainly for confirmation and problem solving. For each patient, a complete three-dimensional fly-through examination was performed in at least three of the four total directions (ie, rectum-to-cecum and cecum-to-rectum for examinations performed with the patient in supine and prone positions). Usually, all four three-dimensional fly-through examinations were performed.
Each CT colonography study was interpreted prospectively by one of the six radiologists (P.J.P., J.R.C.) trained in the primary three-dimensional approach at one of the three participating medical centers. Prior experience in the interpretation of primary three-dimensional CT colonography studies ranged from analysis of 25 studies to analysis of more than 100 studies. The average CT colonography interpretation time, including evaluation of extracolonic structures, was less than 20 minutes (1). Polyps were measured on the three-dimensional scans by using electronic calipers and were recorded by segment (cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, sigmoid colon, or rectum). We believe that polyp measurement is more precise on the three-dimensional endoluminal scan than on the two-dimensional scan, given the ability to optimize the vantage point on the three-dimensional scan. To wit, the average relative size difference for all matched polyps with CT colonography and optical colonoscopy in our study was approximately 10% (P.J.P., unpublished data). Polyp morphology was prospectively assessed as sessile, flat, or pedunculated. Flat polyps were defined as broad-based lesions with a height of less than one-half the polyp width.
Optical Colonoscopy and Interpretation
Optical colonoscopy was performed immediately after interpretation of scans obtained with prospective CT colonography by using standard commercial video colonoscopes (Olympus, Melville, NY). Optical colonoscopy was performed by one of 17 experienced colonoscopists (I.H., W.R.S.), each with several years of experience. The colonoscope was advanced to the cecum and sequentially withdrawn into more distal segments to enable polyp detection. Polyps were measured by using a calibrated linear probe, which has been shown to be more accurate than visual estimation or estimation with biopsy forceps (8). After the colonoscopist completed the evaluation of a segment, a study nurse revealed the CT colonography findings for the previous segment. If a polyp that measured 5 mm or more was detected with CT colonography but not prospective optical colonoscopy, the colonoscopist closely reexamined that segment and was allowed to review a color hard copy of the images obtained with CT colonography for guidance.
Polyp Histologic Analysis
All polyps removed with optical colonoscopy were sent for histologic examination, and each polyp was evaluated by an experienced pathologist. For the purposes of this study, polyps were classified into two broad histologic categories: adenomatous polyps (ie, colorectal neoplasms) and nonadenomatous polyps (ie, all nonneoplastic lesions). Nonadenomatous polyps were further subdivided into hyperplastic polyps, mucosal polyps (ie, lesions with a histologic diagnosis of "normal mucosa"), and other nonadenomatous polyps, which included all polyps with less frequent histologic diagnoses. Diminutive lesions were labeled as "other" if no biopsy specimen was obtained or if the biopsy specimen could not be recovered for histologic evaluation. Unless biopsy specimens were deemed necessary at optical colonoscopy because of diagnostic uncertainty, submucosal lipomas were excluded from consideration.
Statistical Analysis
The 2 test was performed to compare differences in prevalence between adenomatous and nonadenomatous lesions according to polyp size and to compare differences in CT colonography sensitivity for polyp detection. A P value of less than .05 was considered to indicate statistical significance, and a P value of less than .01 was considered to indicate a highly significant difference. CT colonography sensitivity was primarily assessed with by-polyp analysis. Our polyp-matching algorithm requires CT colonography and optical colonoscopy agreement according to polyp size (within a 50% margin of error) and location (within the same or adjacent segment) (1). For the by-patient analysis, a true-positive result for a given polyp size threshold indicates that at least one polyp of that size or larger is present at both CT colonography and optical colonoscopy. Data on adenomatous polyps from this prospective multicenter screening trial, including prevalence and CT colonography sensitivity, are the focus of a separate report; however, they will be applied herein for comparison purposes with nonadenomatous lesions (1).
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Although it is widely recognized that most hyperplastic polyps are small (typically 5 mm), the prevalence of hyperplastic polyps and other nonadenomatous lesions that are 6 mm or larger is not well established (5). Our findings confirm the high frequency of diminutive lesions, which accounted for more than 80% of nonadenomatous polyps. Fortunately, there now appears to be a general consensus (or at least a majority opinion) that diminutive colonic polyps should be regarded as clinically unimportant and ignored at CT colonography (9–11). This sentiment is reflected in recent CT colonography reports that completely excluded diminutive lesions from analysis of CT colonography performance (1,2). In our study, nonadenomatous lesions outnumbered adenomas in the average-risk population by 756 to 554, which differs from findings in CT colonography studies in higher-risk populations, where nonadenomatous lesions comprised only 31%–43% of all polyps (12–14). In our trial, 410 of 1233 patients harbored at least one nonadenomatous polyp. More importantly, however, the results of our study provide an indication of the prevalence of nonadenomatous lesions that are 6 mm or larger in a healthy average-risk population. Although this prevalence rate was less than 10%, it may be surprising to some that nonadenomatous lesions can account for nearly 40% of all polyps that are 6 mm or larger in a screening population.
Because polyp size is the main criterion for action on CT colonography scans, most investigators have reported performance data by grouping adenomatous and nonadenomatous polyps together (2,12–14). While this practice is understandable, some investigators have wisely taken this analysis one step further by separating adenomas from the total polyp group (2,12,13). This information is useful because it allows patient outcome issues to be addressed more directly. Although we are aware of only one prior CT colonography report that has explicitly demonstrated sensitivity for nonadenomatous polyps (12), these data can generally be derived from the information given for total and adenomatous polyps. For example, in the study by Yee et al (13), the derived by-polyp sensitivity for nonadenomatous polyps that are 10 mm or larger is 71% (10 of 14 polyps), which is strikingly similar to our findings (Table 2). Fenlon et al (12) reported a sensitivity of 71% (five of seven polyps) for hyperplastic polyps that measured 6–9 mm, which is also similar to our findings. In the recent study by Johnson et al (2), the pooled sensitivity of three readers for nonadenomatous polyps that were 10 mm or larger was only 44% (16 of 36 polyps), but the pooled sensitivity for adenomas was 46% (38 of 82 polyps). Some investigators did not distinguish adenomatous polyps from total polyps; therefore, nonadenomatous polyp data cannot be inferred (14).
This fortuitous decrease in CT colonography sensitivity for nonadenomatous polyps compared with adenomas has received relatively little attention. One potential explanation for this finding is the tendency of hyperplastic polyps to efface or flatten out with air distention of the colon (12,15). It is likely that polyp morphology itself also plays a role. In our experience, larger nonadenomatous lesions demonstrate an atypical appearance, such as an elongated or flattened shape that exaggerates polyp size relative to polyp volume, more often than adenomas. Furthermore, hyperplastic polyps accounted for the majority of lesions labeled as flat at both CT colonography and optical colonoscopy in our study, which agrees with the experience of others (16). In general, flat lesions are believed to be more difficult to detect with CT colonography than are sessile and pedunculated polyps of similar sizes.
In and of themselves, even large nonadenomatous polyps have little or no direct clinical importance for patients. Rather, their importance with respect to CT colonography screening lies more in their ability to act as false-positive lesions for adenomas. Although CT colonography or optical colonoscopy should not be faulted per se for depicting a large colorectal polyp that is ultimately determined to be nonadenomatous with histologic analysis, these findings are, at the very least, important to consider. For one, cost effectiveness of CT colonography screening hinges in part on the number of optical colonoscopy referrals for polypectomy. In a large optical colonoscopy screening trial, Lieberman et al (17) found that 16.3% of patients without an adenoma had at least one nonadenomatous polyp and that 12.5% of patients had a hyperplastic polyp. Although the sizes of these nonadenomatous lesions were not provided, presumably, most lesions were diminutive. With CT colonography screening, the use of a size threshold analysis for polyp data is critical for interpreting its importance (11). Our findings indicate that, even among adults with an average risk, the number of optical colonoscopy referrals generated for CT colonography–detected nonadenomatous polyps in patients without a substantial adenoma is small and highly dependent on polyp size.
There are several limitations to our study. For instance, optical colonoscopy represents an imperfect reference standard, even when enhanced by our technique of segmental unblinding. It is likely that some polyps were missed at optical colonoscopy, even after CT colonography results were revealed to the colonoscopist. It is also likely that the inherent uncertainty in segmental localization at optical colonoscopy prevented some true polyp matches from being made. Furthermore, anything diagnosed as a polyp at optical colonoscopy was by definition recorded as such, even though a substantial proportion of these lesions revealed only normal mucosa at histologic evaluation. This resulted in some important misdiagnoses at CT colonography that negatively affected sensitivity, including an 8-cm flat "lesion" that was seen at optical colonoscopy and was proved to be normal mucosa. Finally, the sensitivity of CT colonography for detecting diminutive polyps was not reported, since most participating radiologists chose to largely ignore such small lesions, particularly those that were 1–3 mm in size. In actual practice, it is perfectly reasonable—and perhaps even preferable—to ignore such tiny polyps at CT colonography, since these diminutive lesions are of virtually no clinical importance, and optical colonoscopy referral for polypectomy would not be indicated (9–11).
In conclusion, nonadenomatous colorectal polyps are commonly encountered in an average-risk asymptomatic population and outnumber adenomatous polyps, which are the real target for screening. Fortunately, more than 80% of nonadenomatous lesions in our study were diminutive. For colorectal polyps 6 mm or larger, the relative decrease in both CT colonography sensitivity and prevalence of nonadenomatous polyps compared with adenomatous polyps are fortuitous findings and would result in relatively few patients being referred for unnecessary polypectomy.
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FOOTNOTES |
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Authors stated no financial relationship to disclose.
Author contributions: Guarantor of integrity of entire study, P.J.P.; study concepts, P.J.P.; study design, P.J.P., J.R.C.; literature research, P.J.P.; clinical studies, all authors; data acquisition, all authors; data analysis/interpretation, P.J.P.; statistical analysis, P.J.P.; manuscript preparation, definition of intellectual content, and editing, P.J.P.; manuscript revision/review and final version approval, all authors
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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